Osteoarthritis (“OA”), the most common form of arthritis, is a type of arthritis that is characterized by degenerative (gradual deterioration of joint) or abnormal changes in bone, cartilage, and synovium of the joints. OA is often characterized by a progressive wearing down of opposing joint surfaces accompanied at times by inflammation resulting in pain, swelling, and stiffness for the patient. OA can occur in one or more joints following trauma to the joint, following an infection of the joint, or simply as a result of aging. Furthermore, there is emerging evidence that abnormal anatomy, genetics, and obesity may contribute to early development of OA.
Treatment of OA generally involves a combination of exercise, physical therapy, lifestyle modification, and analgesics. Acetaminophen is typically the first line treatment for OA. For mild to moderate symptoms, effectiveness is similar to non-steroidal anti-inflammatory drugs (“NSAIDs”), such as ibuprofen. For more severe symptoms NSAIDs may be more effective. However, while more effective, NSAIDs in severe cases are associated with greater side effects such as gastrointestinal bleeding and renal complications. Another class of NSAIDs, COX-2 selective inhibitors (such as Celecoxib), are equally effective to NSAIDs but no safer in terms of side effects. There are several NSAIDs available for topical use, including diclofenac. Typically, they have less systemic side-effects than oral administration and at least some therapeutic effect. While opioid analgesics, such as morphine and fentanyl, improve pain this benefit is outweighed by frequent adverse events and thus they are not routinely used. Intra-articular steroid injections are also used in the treatment of OA, and they are very effective at providing pain relief, especially in patients exhibiting inflammatory elements of OA. However, the duration of the pain relief is limited to 4-6 weeks and there are adverse effects that may include collateral cartilage damage. If pain becomes debilitating, joint replacement surgery may be used to improve mobility and quality of life. There is no proven treatment to slow or reverse the disease.
For patients who do not get adequate pain relief from simple pain relievers, like acetaminophen or from exercise and physical therapy, intra-articular injections of hyaluronic acid (HA) provide another treatment option to address symptomatic pain and may delay the need for a total joint replacement surgery. It is known that the concentration and molecular weight of native HA is deficient in individuals suffering from OA and therefore joint injections of exogenous HA is believed to replenish these molecules and restore the viscoelastic properties of synovial fluid. It is this property that is responsible for lubricating and cushioning the joints. There is also evidence that HA has biological activity through binding to cell surface receptors and may have a role in mitigating inflammation and cartilage degradation. Regardless of the mechanism of action, pain relief is observed for about six months following a treatment course. A treatment course for HA products on the US market can range from a single injection to others that require 3 to 5 weekly injections to attain this durability of pain relief.
Currently, hyaluronic acid (“HA”) formulations on the market in the United States are commercialized as ready-to-use liquid HA solutions in prefilled syringes. They can be stored at room temperature, and typically have a two year shelf life. While HA of low to moderate molecular weight can be effective, high molecular weight HA formulas can provide additional benefits, especially at higher HA concentrations. However, the HA in solution is known to degrade over time at room temperature, as measured by reduction in HA molecular weight which could impact its efficacy as an OA therapy.
There remains a need for improved methods and compositions for treating joints, and in particular to improved methods and compositions for treating joints using high molecular weight HA, alone or combined with additional components, to address stability and shelf-life problems associated with current treatments.